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Biomedical subjects

T Oki

Publications and source records attributed to T Oki.

At least 397 records · Page 22Linked to original sources
PubMed1980

Biosynthesis of anthracycline antibiotics by Streptomyces galilaeus. I. Glycosidation of various anthracyclinones by an aclacinomycin-negative mutant and biosynthesis of aclacinomycins from aklavinone.

An aclacinomycin-negative mutant strain KE303 which required aklavinone aglycone for the production of anthracycline antibiotics was derived from Streptomyces galilaeus, and employed for the glycosidation of various anthracyclinones. epsilon- gamma- and beta-Rhodomycinones, epsilon-isorhodomycinone, epsilon- and beta-pyrromycinones and chemically modified aklavinones were found to be glycosidated to the biologically active anthracyclines, when they were fed to the growing culture. However, the feeding of daunomycinone, 13-deoxydaunomycinone, adriamycinone and steffimycinone did not yield any glycoside. The bioconversion of presumptive precursor glycosides revealed that aclacinomycin A is biosynthesized by the step-wise glycosidation from aklavinone vai aklavin and MA144 S1.

Aclarubicin↗
PubMed1980

Biosynthesis of anthracycline antibiotics by Streptomyces galilaeus. II. Structure of new anthracycline antibiotics obtained by microbial glycosidation and biological activity.

New anthracycline antibiotics derived from epsilon-, gamma- and beta-rhodomycinones and epsilon-isorhodomycinone by the microbial glycosidation using an aclacinomycin-negative mutant, the strain KE303, of Streptomyces galilaeus MA144-M1 were studied to elucidate their structures and biological activities. These antibiotics were the products in which the anthracyclinones added as precursors were linked at C-7 or C-10 position with the same trisaccharide moiety (cinerulosyl-2-deoxyfucosyl-rhodosaminyl group) as in the parental antibiotic aclacinomycin A. In addition to antimicrobial activity, they exhibited the growth inhibition of cultured L1210 leukemia cells and the marked inhibition against DNA and RNA synthesis.

Animals↗
PubMed1980

[Studies on the absorption, excretion and distribution of aclacinomycin A: absorption, excretion and distribution of 14C- or 3H-aclacinomycin A in mice, rats and rabbits (author's transl)].

A new anthracycline antitumor antibiotic, aclacinomycin A, was labeled with 3H uniformly or with 14C simultaneously at the anthracycline nucleus and L-rhodosamine. These labeled drugs were administered intravenously to normal dd mice, solid type Sarcoma 180 tumor-bearing ICR mice, normal or pregnant Wistar rats and normal rabbits, respectively. 14C-Aclacinomycin A given to rabbits (5 mg/kg) was rapidly cleared from the blood and transferred to tissues. But low level of radioactivity (equivalent to about 0.5 mcg/ml) was remained in the blood even 8 approximately 10 hours after administration. About 45% of the radioactivity were recovered from the urine and 20% from the feces by 72 hours after administration. Tissue levels of 3H-14C-aclacinomycin A given to normal and tumor-bearing mice were highest in the lungs and spleen. Higher distribution was observed also in the liver and kidneys 2 hours after administration. Bioassay revealed that the drug was present in the lungs and spleen in biologically active form and in the liver and kidneys in inactive form, respectively. In the tumor tissue the radioactivity was low but it persisted for 48 hours. Autoradiography with 14C-aclacinomycin A in rats demonstrated that radioactivity due to the drug distributed in the lungs, spleen, kidneys, thymus, intestine, lymph nodes, bone marrow, salivary gland, hypophysis and pineal body but it was rapidly cleared. About 0.2% of radioactivity given to a pregnant rat were transferred to a fetus when 14C-aclacinomycin A was administered intravenously on the 18 approximately 19th day of pregnancy.

Absorption↗
PubMed1980

[Studies on the absorption, excretion and distribution of aclacinomycin A: absorption, excretion and distribution of aclacinomycin A in mice, rabbits and dogs by photometric assay (author's transl)].

An anthracycline antitumor antibiotic, aclacinomycin A, was given to mice, rabbits or dogs intravenously to study the pharmacokinetics by photometric assay based on the absorption of anthracycline ring. The drug was rapidly eliminated from the blood in these animals. Drug levels were much higher in the blood cells than in the plasma. Tissue levels in dogs were 50 approximately 100 times higher than the blood levels, which showed the drug was rapidly transferred from the blood to tissues after administration. Higher levels were observed in the lungs, spleen and lymph nodes, where the drug was present as aclacinomycin A itself and the glycoside-type metabolites that were biologically active. The active form was also detected in the pancreas, heart, thymus, bone marrow and gastrointestinal tract. In the liver and kidneys, biologically inactive aglycone-type metabolites were observed. About 2 approximately 4% of the drug given to rabbits or dogs was recovered in the urine by 72 hours after administration, in which only 10% of the excreted drug was active form in rabbits but about 65% in dogs. The rest was inactive aglycone-type metabolites that were excreted almost in the conjugated form. Biliary excretion also contributed to the total clearance of the drug. Aclacinomycin A was absorbed even by oral administration in rabbits and dogs. Tissue distribution of the drug orally given to dogs was similar to that in intravenous administration, except that higher levels of active form were detected in the gastrointestinal tract and of inactive form in the liver.

Absorption↗
PubMed1980

[Studies on the stability of aclacinomycin hydrochloride. I. Stability of solution of aclacinomycin hydrochloride (author's transl)].

Aclacinomycin is an antitumor anthracycline antibiotic isolated from the culture broth of Streptomyces galilaeus MA144-M1. In this study, the effects of heat, light and pH on the aqueous solution of aclacinomycin hydrochloride (ACM-HCl) were investigated. The following results were found: (1) The kinetic studies revealed that the thermal inactivation of ACM-HCl solution (pH 4.5) was based on the apparent first-order reaction and that Arrhenius equation was confirmed to be established between the rate constants and temperatures. When ACM-HCl solution was stored at 20, 10 and 5 degrees C, the estimated term of ACM-HCl solution at the time when the initial activity (100%) reduced to 90% residual concentration was 1.5, 6 and 12 months, respectively. (2) It was clarified by pH-log k profile that ACM-HCl solution was most stable near at pH 4.5. (3) The higher the buffer concentration was used, the faster the degradation rate, but there was no difference between the residual activity ratios at the various concentrations of ACM-HCl solution. (4) The inactivation of ACM-HCl solution under sunlight occurred in a type of zero-order reaction so that the faster inactivation rates were obtained at the more diluted concentration of ACM-HCl. (5) The major degradation products of ACM-HCl solution were 1-deoxypyrromycin (DP), MA144 S1 (S1) and bisanhydroaklavinone (F1). DP and S1 were mainly found at pH below 4.0 and F1 at pH above 5.0. The degradation under sunlight gave L1 (N-monodemethyl ACM) accompanied by the degradation of aglycone moiety in part.

Aclarubicin↗
PubMed1979

Enzymatic conversion of aclacinomycin A to Y by a specific oxidoreductase in Streptomyces.

A specific oxidoreductase converting aclacinomycin A to a new analog, aclacinomycin Y, was purified to apparent homogeneity from the culture filtrate of aclacinomycin-producing microorganisms. The isolated enzyme was a weakly acidic protein (isoelectric point, 5.9) with a molecular weight of about 72,000. The enzymatic reaction requires molecular oxygen and has a pH optimum at 5.5. The enzyme catalyzed an oxidation of the terminal sugar, L-cinerulose, of the trisaccharide moiety of aclacinomycin A to L-aculose (2,3,6-trideoxyhex-2-enopyranos-4-ulose) with removal of two electrons. Studies of substrate specificity revealed that the enzyme is an oxidoreductase capable of modifying anthracyclic triglycosides by oxidizing their terminal sugars.

Aclarubicin↗
PubMed1979

Antitumor anthracycline antibiotics, aclacinomycin A and analogues. I. Taxonomy, production, isolation and physicochemical properties.

Aclacinomycin A and B, two major components of a new antitumor antibiotic complex, and their 19 analogues were produced by a culture of strain No. MA144-M1, which was identified as Streptomyces galilaeus. They were isolated by chelation with copper ion and silicic acid chromatography, and characterized by physicochemical methods in the anthracycline group of antibiotics.

Antibiotics, Antineoplastic↗